Sanchez1234
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I have ordered DMSO. When it arrives i will begin with 1x per day with 0.5%daro.
Darolutamide (odm-201), A Better Topical Than Enzalutamide?
- Thread starter DavidsDome
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Likewise
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Yeah i thought about liposomal vehicles briefly but i think it would require a lot of hassle and experimentation for not much benefit. Plus an amateur liposomal vehicle would be likely to be greasy as hell and i wouldn't know how it would react with my multiple actives.
Topical RU, minoxidil, ceteizine, nicotinic acid, and caffeine studies were all done without liposomes. And they had no problem with effectiveness.
I don't know how much i can attribute my ongoing success to daro, the high dose ru, or the minoxidil but either way the success keeps coming so i can't really complain, and besides my goal of dropping minoxidil asap (due to aging facial effects), i see no reason to change formulation. It is easy to mix and I'm getting what i want from it.
At this point i am now freely inspecting my hairline under the harshest lighting conditions i can find (which i would have previously avoided) like for example fluorescent public bathroom or office lights. And it still looks great. I am very happy and whatever the cause, more keeps coming. As far as i can tell the rate of continued recovery is on par with when i was on tranny drugs (cypro/spironolactone) and i doubt RU could match these agents. It didn't when i used it at 5%. So i attribute a large amount of the continued success to daro above all else.
I will not be involved in any group buys for the reasons i listed in my "final thoughts" post a bit earlier. This is an experimental unregulated compound with unknown long term safety and it may theoretically be dangerous in my opinion if used irresponsibly by someone living with pregnant women or children. I explained why i went down this path myself. I am comfortable with the risks and i feel i am being responsible about not subjecting anyone else to this chemical by being careful with it. But i don't want to be responsible for anyone else and as I've said I'm not trying to encourage anyone to follow my footsteps. I'm just posting my experiences and things I've learned along the way primarily for academic interest. I hope one day someone does some good research on all this and validates what I'm experiencing on it.
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One more comment I can make on daro at the present time for interest is that I appear to be observing my first side effect which I consider to be a neutral to positive one.
I have been observing this over the past few weeks and monitoring in various climates and it appears to be consistent. My face and scalp are very clearly much dryer and less oily on daro. Dramatically so.
I am of course not applying daro directly to my face. So this implies a facial effect by one of two mechanisms. Either the 10 mg I am applying topically is exerting its effects systemically through the circulation, or it is tracking its way down to my face more locally through the subcutaneous tissues by gravity, contact transfer (eg. From pillow), diffusion, or local circulation. I'm not sure which mechanism is more likely.
When I had my forehead expander implanted, a week later I got a very clear temporary black eye on one side which I was warned about by my surgeon. He said the congealed blood can similarly track down through the face by gravity over time during the recovery period.
Androgens are known to make skin oilier in general. Antiandrogens have the opposite effect. I have commented before on how the daro has made my scalp bone dry even when I apply a lot of topicals that should make it greasy, or even when I sleep in a room that is much too hot.
It is clear the daro is strongly shutting down my sebaceous glands to my scalp with local application. The question is whether it is doing it to my face as well by local tissue tracking, contact transfer, and local circulation (which is fine), or through systemic circulatory androgen blockade.
I'm gonna monitor longer term to see if I can figure it out. I noticed when I was on spironolactone/cypro I had almost no body odor due to the systemic androgen blockade. I will have to try to pay attention if the same is happening here as well. I don't think it is. If I was more sexually active or cared more about my sexual function that might be a good marker as well of what is happening but I am possibly the worst person for judging that. I can at least say my mood and energy are much better on daro than cypro or spironolactone.
Additionally when I took cypro and spironolactone at full tranny doses systemically they did not cause this clear of a drying effect to my scalp or hair. So I think it's almost certainly happening by just spreading naturally under the skin and hitting my face as it tracks and locally circulates or being transferred from my pillow rubbing on my hair then face.
This "side effect" has meant I have required more facial moisturizer but it also has reduced (stopped) my mild intermittent acne and may possibly reduce facial aging over time. So I don't consider this a negative effect at all. I also love that my scalp is so dry as my hair now never looks greasy.
Probably if anything this suggests that applying 0.5% daro 2 ml twice a day is as insane overkill as the math initially suggested. That is fine with me as I want overkill. But this stuff is clearly very very strong. Everything I've read theoretically and my own personal experience so far suggests there's really never been anything like this before.
I have been observing this over the past few weeks and monitoring in various climates and it appears to be consistent. My face and scalp are very clearly much dryer and less oily on daro. Dramatically so.
I am of course not applying daro directly to my face. So this implies a facial effect by one of two mechanisms. Either the 10 mg I am applying topically is exerting its effects systemically through the circulation, or it is tracking its way down to my face more locally through the subcutaneous tissues by gravity, contact transfer (eg. From pillow), diffusion, or local circulation. I'm not sure which mechanism is more likely.
When I had my forehead expander implanted, a week later I got a very clear temporary black eye on one side which I was warned about by my surgeon. He said the congealed blood can similarly track down through the face by gravity over time during the recovery period.
Androgens are known to make skin oilier in general. Antiandrogens have the opposite effect. I have commented before on how the daro has made my scalp bone dry even when I apply a lot of topicals that should make it greasy, or even when I sleep in a room that is much too hot.
It is clear the daro is strongly shutting down my sebaceous glands to my scalp with local application. The question is whether it is doing it to my face as well by local tissue tracking, contact transfer, and local circulation (which is fine), or through systemic circulatory androgen blockade.
I'm gonna monitor longer term to see if I can figure it out. I noticed when I was on spironolactone/cypro I had almost no body odor due to the systemic androgen blockade. I will have to try to pay attention if the same is happening here as well. I don't think it is. If I was more sexually active or cared more about my sexual function that might be a good marker as well of what is happening but I am possibly the worst person for judging that. I can at least say my mood and energy are much better on daro than cypro or spironolactone.
Additionally when I took cypro and spironolactone at full tranny doses systemically they did not cause this clear of a drying effect to my scalp or hair. So I think it's almost certainly happening by just spreading naturally under the skin and hitting my face as it tracks and locally circulates or being transferred from my pillow rubbing on my hair then face.
This "side effect" has meant I have required more facial moisturizer but it also has reduced (stopped) my mild intermittent acne and may possibly reduce facial aging over time. So I don't consider this a negative effect at all. I also love that my scalp is so dry as my hair now never looks greasy.
Probably if anything this suggests that applying 0.5% daro 2 ml twice a day is as insane overkill as the math initially suggested. That is fine with me as I want overkill. But this stuff is clearly very very strong. Everything I've read theoretically and my own personal experience so far suggests there's really never been anything like this before.
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I read somewhere that this could potentially change your balding pattern for the better so if you stop using it you might not lose any hair, sounds like the cure to me.
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Edit : I just read your 2nd post.
So using 0.5% twice a day does the trick.
For people who can afford it, using 0.25% could allow the same thing at a lower cost.
I'm waiting 2k19 like a child : Fevipiprant and Daro will be at bargain prices!
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ebay
Sanchez1234
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Read all pages, when you see the beautiful name LUO you have found the pot of gold.
Sanchez1234
Experienced Member
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@IdealForehead
Due to my hairstyle i can only do topicals once a day. What are your thoughts on only applying 0.5% at night?
Due to my hairstyle i can only do topicals once a day. What are your thoughts on only applying 0.5% at night?
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Looking at the half life, I would say that once a day should be fine.
The question is more if the dose will be sufficient for you, I think.
The question is more if the dose will be sufficient for you, I think.
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I've tried to answer your question by starting with something I wrote previously in this thread and developing it more fully. I've tried to research it further with data and extrapolate some numbers to give an idea of how well this will work.
The short answer is it should be fine.
Factors Determining Dose and Frequency of Topical Administration
The dose and frequency with which a topical compound must be applied to be effective is determined by 3 questions:
- How much compound is needed to flood all the target receptors of the dermal papillae throughout the scalp?
- How long will the compound remain bound to the target receptors before it is 'washed' or diffuses away out of the scalp? (likely defined primarily by receptor affinity, blood supply, and vehicle composition)
- How quickly is the compound degraded in the skin?
Topical vs. Systemic Half Lives
Question two and three together essentially define the "topical half life" - how quickly a compound either leaves or is broken down within the skin. Although in principle, one might presume the topical half life can be inferred by the usual published half life statistic of the compound, the published "half life" is almost universally going to be for oral administration, and the topical half life is not the same as the oral half life.
The oral half life generally refers to the time for a compound's BLOOD LEVELS to be cut in half. This represents usually how fast the liver degrades the compound. But for topical application, we do not care what the blood levels are or what the liver does, except with the interest of reducing side effects through hopefully short serum half life. In an ideal world, the blood levels would always be zero.
We care for topical application more about how fast the skin can degrade it. And this is almost impossible to answer for most compounds, as it is not something that is commonly studied.
However, we can perhaps draw conclusions from other better studied compounds. In general, the principle is that the liver will always degrade compounds faster than the skin, as the liver is an enzymatic powerhouse designed for detoxification, while skin cells simply don't have this capacity. Skin cells are meant to exist primarily as just a barrier from our environment. They can't do that much else very well.
(i) Minoxidil
We know the oral half life for minoxidil is 4.2 hours. I cannot find the original research to support this, but Bernstein states that the topical half life (time to degrade in the skin) for minoxidil is 22 hours. So we can see the topical half life is 5.2x longer than the oral.
With a 22 hour topical half life, minoxidil is still more effective according to the company that developed it with twice daily application, as this creates smoother levels.
(ii) Retinoic Acid
Retinoic acid is well studied as well for both skin and oral use in acne treatment. It has an oral half life of 45 minutes and a topical half life of around 2-2.5 hours. So again we're seeing somewhere around 2.6-3.3x longer duration in the skin than the blood. (ref, ref, ref)
It seems from the free full text of this study that the enzymes which commonly degrade these kinds of pharmaceuticals are expressed to varying extents in different tissues, and thus different tissues will break down target compounds in different ways to different breakdown products. They describe a software called Metasite that lets you predict breakdown products based on specified tissues: liver, skin, and brain.
Conclusion
We therefore can't directly use oral half lives (liver metabolism) to predict topical half lives (skin metabolism). However, we can perhaps in general expect topical half lives to be in the range of 2.6-5.2x the oral half life.
In this case, darolutamide has an oral half life of 15.8 hours, with an equally powerful product made from this (at least by liver metabolism - no guarantee what gets made by skin metabolism) lasting another half life of 10 hours. This would suggest the compound probably has a skin half life of at least 45-60 hours (2-3 days). In this case, once a day application should therefore be absolutely fine.
If the darolutamide degrades in the skin via the same pathway as in the liver, to ORM-15341, or you're just being optimistic in general, you could probably even get away with applying every two days.
Interestingly enough, using this type of "rule of thumb" may also provide further evidence for weakness of RU58841. RU58841 has an serum half life of only one hour. If we can guess that the skin is ~5x slower to break it down, this might suggest a topical half life of 5 hours. This is probably much too short to be ideal. It could explain some inadequate results we've seen on the compound, especially if applied only once daily. It might also explain why I have found I must apply in high doses and twice a day to keep the "male pattern baldness itch" at bay.
Compounds with too short a serum half life (like RU58841) will almost universally avoid systemic side effects, but likely will degrade too quickly in the skin as well to get the desired effect. There is a balance that exists between half life, effectiveness, and side effects.
I think daro strikes this balance nicely, probably even once daily. And I think I just coincidentally talked myself out of continuing RU58841.
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Further Notes About Skin Dryness
One more note. I researched the skin dryness I am experiencing and it definitely appears to be plausible and expected outcome of overly aggressive local androgen blockade.
I found a study of flutamide vs. finasteride 5 mg for PCOS in women. Flutamide is like daro an androgen receptor antagonist but much weaker. This study stated: "Dry skin appeared significantly more with flutamide (67.3%) than with finasteride (23.6%)."
Another study states: "skin dryness probably related to the flutamide action mechanism inhibiting the sebum production".
So I think this is a clear indication the daro is in fact completely neutering my scalp so much that sebum production has stopped dead! The skin is starting to flake a bit from the dryness even which is no big deal but kind of impressive when you take into account what it means. I will try to manage this with more conditioner when I shower, and if that doesn't do it, I may cut back on the dose as it's probably very much insanely overkill.
The analysis I posted one post above probably suggests that the reason we have seen failures on RU58841 has more to do with its inadequate topical half life, and less to do with a lack of potency. 0.1% daro should beat RU58841 in potency of inhibition, but roughly be in the same "strength range". However, unlike RU, 0.1% daro should provide very long lasting effects.
I doubt higher than 0.1% daro is going to be necessary, even once daily.
As a tangential note, this daro effect has given me the idea to try an application of maybe 0.25 mL 0.1% daro once daily to each underarm after showering to see if it shuts down my underarm body odor. Could be nice. Who needs body odor? I will start that tonight - which will be daro experiment #2.
One more note. I researched the skin dryness I am experiencing and it definitely appears to be plausible and expected outcome of overly aggressive local androgen blockade.
I found a study of flutamide vs. finasteride 5 mg for PCOS in women. Flutamide is like daro an androgen receptor antagonist but much weaker. This study stated: "Dry skin appeared significantly more with flutamide (67.3%) than with finasteride (23.6%)."
Another study states: "skin dryness probably related to the flutamide action mechanism inhibiting the sebum production".
So I think this is a clear indication the daro is in fact completely neutering my scalp so much that sebum production has stopped dead! The skin is starting to flake a bit from the dryness even which is no big deal but kind of impressive when you take into account what it means. I will try to manage this with more conditioner when I shower, and if that doesn't do it, I may cut back on the dose as it's probably very much insanely overkill.
The analysis I posted one post above probably suggests that the reason we have seen failures on RU58841 has more to do with its inadequate topical half life, and less to do with a lack of potency. 0.1% daro should beat RU58841 in potency of inhibition, but roughly be in the same "strength range". However, unlike RU, 0.1% daro should provide very long lasting effects.
I doubt higher than 0.1% daro is going to be necessary, even once daily.
As a tangential note, this daro effect has given me the idea to try an application of maybe 0.25 mL 0.1% daro once daily to each underarm after showering to see if it shuts down my underarm body odor. Could be nice. Who needs body odor? I will start that tonight - which will be daro experiment #2.
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Hopefully Darolutamide becomes cheap very quickly from yours and some others success on it.
@IdealForehead Could this as a topical anti-androgen have effect on muscle growth/mass and strength as it is so strong ?
It has trouble crossing the into the blood brain barrier, so no shouldnt, you might have local side effects like your face, hair, and scalp.
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Absolutely, in my opinion, that's very possible! It would depend on how much you are applying and how much is absorbing systemically vs. being degraded in the skin, which is again all speculative. But definitely if sufficient quantity absorbs in the blood it can block the androgen receptors of your muscles and inhibit test/DHT from encouraging muscle growth.
Daro is something that would have to be titrated very carefully to the lowest effective dose long term. It might be 0.1% once daily. It might be 0.05% once daily. It might even be 0.01%! Who knows?
Keep in mind the oral castration dose is 600 mg twice daily, and I am applying 10 mg twice daily which despite being 1.6% of the oral castration dose, is apparently completely castrating my scalp to the point of the sebum production shutting down. The hope is most hits the scalp and not the rest of the body too much, but there is no guarantee of that. My face as noted is drying as well, and I am not applying directly to that at all.
@Jonnyyy the fact that it only minimally crosses the blood brain barrier should more mean that it therefore won't block androgens from binding in the brain too much. So people on daro probably won't as often get mood/cognitive side effects like "brain fog" or depression. Gyno rates were almost nonexistent in the studies done for this reason as well. I'm guessing there will fewer sexual side effects on daro too, even orally, as I think "sex" comes mostly from the brain, but that's just my theory.
Personally, I'm not too worried about any of that. My muscles have never been impressive and my mood/energy feels great on daro (vs. cypro/spironolactone). Funny enough, my biggest worry is now surprisingly becoming this drying effect, although it's only slightly a worry right now. I don't worry about a dry scalp. But I already suffer a bit from dry eyes. I've just read that androgen deprivation can worsen dry eyes (ref). I'm probably getting ahead of myself but I'm betting I'm gonna need to either drop my daro dose or figure out a topical solution to keep my eyes from drying out like my face/scalp already has. Probably just dropping the daro dose will do. I'll cross that bridge when I get to it. My hair is still growing back and I'm tolerating it, so the scorched earth policy continues for now ...
Androgen deprivation can have all sorts of funny effects on the body and it can be different for different people. Absolutely with something this strong, my goal is the absolute lowest effective dose.
I am definitely feeling like using darolutamide to solve hair loss is kind of like using an atomic bomb to kill a mouse. It will definitely kill the mouse. But if you want to limit collateral damage, care is needed, and unfortunately at the present there are no clear dosing guidelines or studies to help direct things, so it can be risky.
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In the way things are man, we whether kill that moist with an atomic bomb or we do close to nothing and watch him thrive, about how much does it cost you daily (not including the other relatively cheap chemicals)
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Well I can definitely say atomic bomb or not, it feels good to kill that mouse.
finasteride/dutasteride/RU failed me, and only spironolactone/cypro/daro have had the desired effects. Of those, daro is by far my favorite both for potency and side effect profile. Based on my limited experience with oral cypro 100 mg/day, oral spironolactone 200 mg/day, and topical daro, topical daro is almost certainly the strongest of the three. Topical daro is seeming to completely neutering my scalp in a way that spironolactone/cypro were not as capable of doing, and with much fewer mood/energy side effects.
I am using 10 mg twice daily of darolutamide. At $2000 for 5 grams from Luo, this is costing me roughly $8 USD per day. Almost certainly, this is both overkill in terms of the dose I am applying and the frequency of administration. I would guess 5 mg once a day at $2 USD per day should be adequate for most men. Probably 5 mg applied every other day, at a cost of $1 USD per day, would even be adequate for most men.
So actually this stuff probably has the potential to be much cheaper than RU58841 for a dramatically better effect.
But being so strong, the risk of side effects is very real, especially with long term use or if using very high doses. A low dose of systemic darolutamide over the next 50 years (my planned duration) could have real consequences. People shouldn't be delusional about the potential. That is again partly why I am not encouraging anyone else to use this though I am using it myself.
I think the following is a really good article summarizing potential risks, as it is based on use of androgen deprivation in sex offenders who are otherwise physically healthy young men (unlike prostate cancer patients who are usually old and dying):
Potential Side Effects of Androgen Deprivation Treatment in Sex Offenders
To quote a section from the abstract:
I will be reducing my dose to the lowest I can get away with over time. This stuff is not a joke.
finasteride/dutasteride/RU failed me, and only spironolactone/cypro/daro have had the desired effects. Of those, daro is by far my favorite both for potency and side effect profile. Based on my limited experience with oral cypro 100 mg/day, oral spironolactone 200 mg/day, and topical daro, topical daro is almost certainly the strongest of the three. Topical daro is seeming to completely neutering my scalp in a way that spironolactone/cypro were not as capable of doing, and with much fewer mood/energy side effects.
I am using 10 mg twice daily of darolutamide. At $2000 for 5 grams from Luo, this is costing me roughly $8 USD per day. Almost certainly, this is both overkill in terms of the dose I am applying and the frequency of administration. I would guess 5 mg once a day at $2 USD per day should be adequate for most men. Probably 5 mg applied every other day, at a cost of $1 USD per day, would even be adequate for most men.
So actually this stuff probably has the potential to be much cheaper than RU58841 for a dramatically better effect.
But being so strong, the risk of side effects is very real, especially with long term use or if using very high doses. A low dose of systemic darolutamide over the next 50 years (my planned duration) could have real consequences. People shouldn't be delusional about the potential. That is again partly why I am not encouraging anyone else to use this though I am using it myself.
I think the following is a really good article summarizing potential risks, as it is based on use of androgen deprivation in sex offenders who are otherwise physically healthy young men (unlike prostate cancer patients who are usually old and dying):
Potential Side Effects of Androgen Deprivation Treatment in Sex Offenders
To quote a section from the abstract:
Earlier thought of as a sex hormone only, testosterone has been increasingly shown to have manifold actions in the adult male. Normal adult levels of androgens are required for the health of bones, a large number of metabolic functions, mood, erythropoiesis, sebaceous gland activity of the skin, and several other functions. Severe androgen deficiency is associated with pathologies of these biological systems. Androgen deprivation therapy may result in osteoporosis, weight gain with an increased visceral adiposity, impaired glucose tolerance, dyslipidemia, and emotional disturbances. Some of these features combine in the metabolic syndrome that is also frequently associated with the use of psychotropic medication in general. It leads to a moderately increased risk of fractures and diabetes mellitus (by 40%–50%), and a small increased risk of cardiovascular morbidity and depression (by 10%–20%). It should be noted that small proportionate increases in risk may be of modest clinical significance when background risks are very low. Effective and safe management of sex offenders treated with testosterone-deprivation therapy should include careful monitoring of side effects and their prevention and treatment.
I think the risks of depression and mood effects are lower with darolutamide due to it not crossing the blood-brain barrier, but absolutely all the other risks would still apply. You wouldn't notice these things in the short term, but over decades, perhaps. They also list the following as less commonly considered potential effects, including what I am already experiencing in terms of dry skin and potentially eyes:
Profound androgen deprivation therapy (ADT) reduces sebaceous gland activity in the skin, often leading to dry skin and brittle nails.54 Symptoms such as itching and skin tears can be very bothersome. They usually can be remedied by topical application of moisturizing creams. Moreover, facial and body hair growth is reduced by ADT (i.e., feminization).4
Other side effects that have been described are migraine, leg (muscle) cramps, phlebitis, vertigo, elevation of blood pressure, gastrointestinal complaints, gallbladder stones, thromboembolic complications (deep vein thrombosis).10,55 Besides impotence and its libido-reducing effects, ADT also directly induces partial azoospermia and infertility.
Other side effects that have been described are migraine, leg (muscle) cramps, phlebitis, vertigo, elevation of blood pressure, gastrointestinal complaints, gallbladder stones, thromboembolic complications (deep vein thrombosis).10,55 Besides impotence and its libido-reducing effects, ADT also directly induces partial azoospermia and infertility.
I will be reducing my dose to the lowest I can get away with over time. This stuff is not a joke.
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It would be great if say, after 6 months or a year, you could test in the blood for the presence of molecule and metabolites. That way we would know for sure, how great of a risk it is. Because measuring hormones would not tell you anything, the only way to know is to test for the molecule itself.